Chronic myeloid leukemia (CML) is a blood cancer predominantly affecting older adult patients. According to the American Cancer Society, an estimated 8,860 people will be diagnosed with CML in 2022. Treatments for CML have evolved with a focus on CML phase severity or progression. Overall, there have been some breakthrough treatment options for a high percentage of patients with CML. This is largely due to the discovery of tyrosine kinase inhibitors (TKI); however, drug resistance continues to present a significant challenge in the management of CML disease. The use of interferon (IFN), antimetabolites, and bone marrow transplants provides alternative treatment options, but also presents limitations, including severe side effects, toxicity, and graft versus host disease. Nanomedicine has demonstrated benefits in terms of efficacy, often reducing or eliminating unwanted toxicities associated with the use of conventional drug agents. This review summarizes rational molecular targets of CML drugs and provides highlights of current FDA-approved agents for the treatment of CML. Additionally, this communication includes an overview of the limitations of conventional treatments and how nanomedicine has addressed challenges encountered during CML treatment.